POS0635 METHOTREXATE MAINTENANCE ONE YEAR AFTER INITIATION OF A FIRST TARGETED THERAPY: RESULTS OF THE PROSPECTIVE STRATEGE 2 STUDY
Authors: C. Gaujoux-Viala, E. Dernis, E. Senbel, H. Herman-Demars, J. Becker, A. Courbeyrette, R. M. Flipo
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Methotrexate (MTX) is the first line standard of care for the management of rheumatoid arthritis (RA). In the event of an inadequate response to MTX and the presence of a poor RA prognosis factor, recommendations include initiation of biological (bDMARD) or synthetic (tsDMARD) targeted therapy in combination with MTX. <h3>Objectives</h3> STRATEGE 2 aims to establish the maintenance of MTX within two years of initiating a first targeted therapy. <h3>Methods</h3> STRATEGE 2 is a non-interventional study including RA patients treated with MTX for at least 3 months and requiring initiation of a first b/tsDMARD due to disease activity. The primary endpoint is maintenance of MTX unchanged within 12 months of initiation of targeted therapy. Non-maintenance is defined as: permanent discontinuation of MTX and/or dose reduction and/or transition from the subcutaneous route (SC) to oral (PO). Then, univariate and multivariate analysis was applied to identify potential predictors of MTX maintenance. <h3>Results</h3> Between Feb. 2019 and Dec. 2020, 53 French sites included 186 RA patients. Among them, data from 180 patients were analysable: 73.4% female, mean age 56.4 ±13.6 years, mean diagnostic oldness of 5.6 ±7.2 years, MTX treatment since 4.3 ±5.3 years, 71.7% via SC and the average dose was 19.9 ±3.9 mg/wk. The mean DAS28 score was 4.3 ±1.2 and the mean HAQ score was 1.0 ±0.7. At the end of the inclusion consultation, rheumatologists initiated a first targeted therapy: 8.6% by bDMARDs (anti-TNF: 58.4%, anti-IL6: 12.7%, Abatacept/Rituximab: 18.5%) and 10.4% by tsDMARDs. MTX was maintained unchanged in 76.1%, changed in 21.7% and stopped in 2.2% of the cases. The changes consisted of a dose reduction to 13.8 ±3.8 mg/wk for 19.4% of patients and a pathway change for 31.4% (from SC to PO). Approximately 12 months (377.8 ± 41.5 days) after initiation of targeted therapy, 95% of patients completed a follow-up visit (N=171). Of these patients, 6.4% had discontinued targeted therapy, 85.9% were on bDMARD (anti-TNF: 50.3%, anti-IL6: 12.8%, Abatacept/Rituximab: 22.8%) and 14.1% on tsDMARD. The average MTX dose was 18.0 ±4.2 mg/wk and MTX was administered SC for 59.4% of patients. According to the composite endpoint definition, MTX was maintained for 40.9% of patients. Non-maintenance was represented by 30% discontinuation, 44% of patients with a dose decrease only, 3% of patients with only a change in route of administration (from SC to PO) and 23% of patients with the two strategies. Using univariate analysis, three factors were selected for the multivariate: age (p=0.009), physicians' mode of practice (p=0.096) and patients who estimate having completely participated in the decision-making for the targeted therapy (p= 0.197). Only age was significative (OR=1.06, 95%CI [1.03,1.10], p&lt;0.001), decision-making shows a strong trend (p=0.052) and both characteristics were adjusted on the mode of practice (p=0.256). <h3>Conclusion</h3> There are many therapeutic adaptations in the year following the initiation of b/tsDMARD. Twelve months after the introduction of b/tsDMARD, more than 8 out of 10 patients retained MTX as a combination therapy. Nearly 46% of patients had an adaptation of this treatment (dose reduction and/or return to the PO route). These practices are in line with the latest EULAR guidelines [1] which recommend the association of b/tsDMARDs with MTX. <h3>Reference</h3> [1]Smolen JS, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis 2023;82:3–18. <h3>Acknowledgements</h3> The authors wish to acknowledge RCTs for their contribution to the statistical analysis, the investigators, centres and patients. <h3>Disclosure of Interests</h3> Cécile Gaujoux-Viala Consultant of: AbbVie; Amgen; Boehringer Ingelheim, Bristol-Myers Squibb; Celgene; Eli Lilly; Galapagos; Gilead Sciences, Inc.; Janssen; Medac; Merck-Serono; Mylan; Nordic Pharma; Novartis; Pfizer; Roche; Sandoz; Sanofi; and UCB Pharma., Grant/research support from: AbbVie; Amgen; Boehringer Ingelheim, Bristol-Myers Squibb; Celgene; Eli Lilly; Galapagos; Gilead Sciences, Inc.; Janssen; Medac; Merck-Serono; Mylan; Nordic Pharma; Novartis; Pfizer; Roche; Sandoz; Sanofi; and UCB Pharma., Emmanuelle Dernis Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, MSD, Nordic Pharma, Novartis, Pfizer, Roche, Roche-Chugaï, Sandoz, Sanofi and UCB Pharma., Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, MSD, Nordic Pharma, Novartis, Pfizer, Roche, Roche-Chugaï, Sandoz, Sanofi and UCB Pharma., Eric Senbel Consultant of: Abbvie, Amgen, Biogen, Celltrion, Fresenius Kabi, Janssen, Lilly, MSD, Nordic Pharma, Pfizer, Roche-Chugai and Sandoz, Sanofi., Hélène Herman-Demars Employee of: Nordic Pharma France, Jennifer Becker Employee of: Nordic Pharma France, Agnès Courbeyrette Employee of: Nordic Pharma France, René-Marc Flipo Consultant of: Abbvie, Bristol-Myers Squibb, Eli-Lilly, Janssen, MSD, Nordic-Pharma, Novartis, Pfizer, Roche-Chugaï, Sandoz and Sanofi., Grant/research support from: Abbvie, Bristol-Myers Squibb, Eli-Lilly, Janssen, MSD, Nordic-Pharma, Novartis, Pfizer, Roche-Chugaï, Sandoz and Sanofi.